Accelerating reactions with microreactors at elevated temperatures and pressures: Profiling aminocarbonylation reactions
Accelerating reactions with microreactors at elevated temperatures and pressures: Profiling aminocarbonylation reactions
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DOI：
10.1002/anie.200604175
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Jensen, Klavs F.
中科院分区：
文献类型：
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作者：
Murphy, Edward R.;Martinelli, Joseph R.;Jensen, Klavs F.
微反应器的使用可以大大加速反应条件的扫描和优化，因为它增强了热量和质量传递，减少了反应体积，并且能够在密封系统内运行多个实验（最大限度地减少氧气和水的污染）。在过去的十年中，在实验室规模合成中通常使用的条件下进行的几项研究已经证明了这些优点。[1-10]微反应器的主要优点是能够在常规玻璃器皿中不容易实现的条件下进行反应，例如在升高的温度和压力下使用标准溶剂（例如甲苯）。[4，9]在这些条件下进行的反应是微波合成的主要优点之一。[11微反应器提供了微波反应器的许多优点，并且具有连续流动的附加优点，并且它们不需要微波发生器。在玻璃基微反应器中实现高压由于与流体入口和出口管接口的困难而变得复杂。例如，玻璃和硅器件的典型的压缩密封技术是麻烦的，并且它们通常限于中等压力（约100 MPa）。10 bar），以避免损坏设备。在本文中，我们使用最近开发的基于焊料的密封技术[5]来构建能够达到超过100巴的压力的微反应器[13]，并证明在Heck氨基羰基化[14]反应中在甲苯沸点以上操作的潜在优势（方案1）。微反应器的使用使得能够快速评估反应条件的改变对产率和选择性的影响，以及使用快速连续的几种试剂溶液的实验。快速改变反应物和条件的能力将是高通量合成各种化合物以及催化剂筛选的有力策略。化学参数如官能团、配体性质和碱强度可随着反应条件沿着迅速变化。反应参数的连续操作和扫描提供的信息可以导致对典型的基于批处理或阵列的过程的更好的了解，这些过程通常限于一次一个变量的实验。该案例研究还说明了封闭系统在处理高压有毒气体（一氧化碳）和空气敏感Pd催化剂方面的优势。微反应器（图1）是通过光刻定义混合器和通道布局，然后在硅中蚀刻通道，在硅中形成的。[4]随后硅的氧化在表面上形成玻璃层，使得当通过将Pyrex玻璃晶片结合到氧化硅装置来覆盖通道时，反应通道在功能上变得等同于玻璃反应容器。此外，顶部玻璃层提供了对反应介质的视觉访问，
The use of microreactors can greatly accelerate scanning and optimization of reaction conditions because of enhanced heat and mass transfer, reduced reaction volumes, and the ability to run several experiments within a sealed system (minimizing contamination by oxygen and water). These advantages have been demonstrated in several studies over the past decade at conditions typically used in bench-scale synthesis.[1–10] A major advantage of microreactors is the ability to perform reactions under conditions that cannot be easily realized in conventional glassware, such as the use of standard solvents (eg toluene) at elevated temperatures and pressures.[4, 9] Reactions performed under these conditions is one of the major benefits of microwave synthesis.[11, 12] Microreactors offer many of the advantages of microwave reactors and have the additional advantages of continuous flow and that they do not require a microwave generator. The realization of high pressure in glass-based microreactors is complicated by difficulties in interfacing with fluid inlet and exit tubes. For example, typical compression sealing techniques of glass and silicon devices are cumbersome, and they are typically limited to moderate pressures (ca. 10 bar) to avoid breaking the device. Herein we use a recently developed solder-based sealing technique [5] to construct microreactors capable of reaching pressures exceeding 100 bar [13] and to demonstrate the potential advantages of operating above the boiling point of toluene in Heck aminocarbonylation [14] reactions (Scheme1). The use of microreactors enables rapid evaluation of the effects of modifications to the reaction conditions on yield and selectivity, as well as the use of experiments with several reagent solutions in rapid succession. The ability to rapidly change reactants and conditions would be a powerful strategy for the highthroughput synthesis of a diverse array of compounds as well as for catalyst screening. Chemical parameters such as functional groups, ligand properties, and base strength could be rapidly varied along with reaction conditions. The continuous operation and scanning of reaction parameters provides information that can lead to improved insight over typical batch-or array-based processes, which are often limited to one-variable-at-a-time experimentation. The case study also illustrates the advantages of a closed system in handling elevated pressures of a toxic gas (carbon monoxide) and air-sensitive Pd catalysts.The microreactor (Figure1) is formed in silicon by defining the mixer and channel layout by lithography and then etching channels in silicon.[4] Subsequent oxidation of silicon forms a glass layer on the surface so that when the channels are capped by bonding a Pyrex glass wafer to the oxidized silicon device, the reaction channels become functionally equivalent to a glass reaction vessel. Moreover, the top glass layer provides visual access to the reaction medium,